Protease-containing liquid detergent compositions are well known. A commonly encountered problem, particularly with heavy duty liquid laundry detergents, is the degradation by protease enzyme of second enzymes in the composition, such as lipase, amylase and cellulase. The performance of the second enzyme upon storage and its stability in product are thus impaired by the presence of protease in the liquid detergent product.
Boronic acids are known to reversibly inhibit protease. This inhibition of protease by boronic acid is reversible upon dilution, as occurs in wash water.
It is difficult to find an effective reversible protease inhibitor which is stable over time in a liquid detergent product. A search for a boronic acid which is a good reversible serine protease inhibitor and does not lose efficacy in product over time has now led to the synthesis of a novel compound of the structure described below. A new method for synthesizing .beta.-aminoalkyl and .beta.-N-peptidylaminoalkylboronic acids is also described below. Lastly, a new use for the subject compound or its derivatives as an effective serine protease inhibitor in a liquid detergent composition containing serine protease is described below.
Certain boronic acids are cited as subtilisin inhibitors in Phillip, M. and Bender, M. L., "Kinetics of Subtilisin and Thiosubtilisin", Molecular & Cellular Biochemistry, vol. 51, pp. 5-32 (1983), and in Phillip, M. and S. Maripuri, "Inhibition of Subtilisin by Substituted Arylboronic Acids", FEBS Letters, vol. 133(1), pp. 36-38 (October, 1981). Many of these inhibitors, however, are arylboronic acids, which owing to protodeboronation may not be stable under the slightly alkaline conditions found in many liquid detergents. It is believed that alkylboronic acids, particularly those with atoms other than hydrogen on the .alpha. carbon, may not possess the desired stability due to autoxidation as discussed by Johnson, J., Van Campen, M., and Grummitt, O., Journal of the American Chemical Society, vol. 60, 111-115 (1938).
Known synthetic routes to prepare boronic acid compounds have been reviewed by D. Matteson in The Chemistry of the Metal Carbon Bond, vol. 4, chapter 3, pp. 307-409, edited by F. Hartley (1987) and in Tetrahedron, vol. 45, pp. 1859-1885 (1989). Most of the references cited in Matteson's review articles and in the review on the use of catecholborane by C. Lane and G. Kabalka, Tetrahedron, vol. 32, pp. 981-990 (1976) are to the hydroboronation of olefins that lack heteroatom substitution. Only one reference could be found which is relevant to the formation of a boronic acid possessing the nitrogen heteroatom two carbons removed (i.e. .beta.) from boron: Butler, D. and Soloway, A., Journal of the American Chemical Society, vol. 88, pp. 484-487 (1966). These authors demonstrated that it was possible to form .beta.-ureidoethyl and .beta.-carbamidoehylboronic acids from the corresponding N-vinyl urethan, and N-vinyl urea in three steps by hydroboration with borane followed by oxidation and hydrolysis. Later, Dicko, A., Montruy, M., and Baboulene, M. published on the formation of .gamma.-aminoboronic acids in Synthesis Communications, vol. 18, pp. 459-463 (1988). Synthesis of .alpha.-N-peptidylaminoboronic acids is described in EP 0293-881, Kettner, published December 7, 1988.
The novel compounds and method of synthesis herein have not yet been described, nor have liquid laundry detergents containing them.